Isothioureas, cyclocondensation with

Analogous to the TOSMIC reactions is the cyclocondensation of an isothiourea with the enolate of ethyl isocyanoacetate (12) to give an alkyl 5-aminoimidazole-4-carboxylate (13). This regioselective synthesis provides... 

Regiochemical synthesis of 1-substituted imidazole-4-carboxylates can be achieved by treatment of a (Z)-)3-dimethylamino-of-isocyanoacrylate with an alkyl or acyl halide (see Section 2.1.1 and Scheme 2.1.8), by cyclization of 3-alkylamino-2-aminopropanoic acids with triethyl orthoformate followed by dehydrogenation of the initially formed imidazoline (see Section 3.1.1 and Scheme 3.1.2), by condensation of 3-arylamino-2-nitro-2-enones with ortho esters in the presence of reducing agents (see Section 3.1.1 and Scheme 3.1.4), by reaction of an alkyl A -cyanoalkylimidate with a primary amine (see Section 3.2 and Scheme 3.2.1), the poor-yielding acid-catalysed cyclization of a 2-azabutadiene with a primary amine (see Section 3.2 and Scheme 3.2.3), the cyclocondensation of an isothiourea with the enolate form of ethyl isocyanoacetate (see Section 4.2 and Scheme 4.2.5), and from the interaction of of-aminonitrile, primary tunine and triethyl orthoformate (see Chapter 5, Scheme 5.1.5, and Tables 5.1.1 and 5.1.2). 

Cyclocondensation of substituted isothiocyanates 24 with amidines, isoureas, isothioureas or guanidines provides 1,3,5-triazine-2(1 //j-thiones 25 in good yield.433 43s Generally, aroyl isothiocyanates and imidoyl isothiocyanates are employed. 

Orotic acid is the key compound in the biosynthesis of almost all naturally occurring pyrimidine derivatives. Its synthesis is achieved by cyclocondensation of diethyl 2-oxobutanedioate with iS-methyl-isothiourea, followed by direct or oxidative hydrolysis of the 2-methylsulfanyl intermediate 27 ... 

Pyrimidines are an interesting class of nitrogen-containing heterocycles which display a broad range of useful properties.Based on a novel cyclocondensation reaction between acetylenic ketones of type 339 and polymer-bound isothiourea 338, Obrecht et developed a versatile and efficient solid-phase synthesis of polymer-bound 2-(alkylthio)-4,6-disubstituted pyrimidines 340, and combined this protocol with the nucleophilic displacement reaction of the 2-sulfonyl group of pyrimidines 47 j gy dgavage reaction. In addition, simple... 

Starting from Wang resin 558,5 equiv of Fmoc-amino acid 559,5 equiv of DIC, and 0.1 equiv of DMAP in DMF shaken at room temperature for 12 h facilitated the initial loading (Scheme 9.66). After deprotection with 20% piperidine in DMF, resin 560 was treated with 10 equiv of diketene 561 and 0.1 equiv of DMAP in DCM at 0°C for4h to afford the amide resin 562. This was then exposed to 10 equiv of 4-methyl benzaldehyde 563 in the presence of 0.5 equiv of piperidine and acetic acid (both 1M in toluene) and heated at 80°C for 4h to afford intermediate 564. Cyclocondensation was achieved with 5 equiv of isothiourea hydrochloride 565 and 6 equiv of CS2CO3 in NMP heated at 80°C for 24 h to produce the pyrazine core 566. Cleavage from the resin was carried out in TFA H20 TIPS (95 2.5 2.5) to produce 567. 

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